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Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used IMR90 ER:RAS cells infected with an empty vector or an shRNA for ARID1B and induced senescence by addition of 4OHT. 6 days later RNA was collected for gene expression analysis. With a functional screen we previously identified ARID1B as a new regulator of cellular senescence. By performing gene expression analysis we confirmed this finding and showed that knockdown of ARID1B prevents the expression of genes induced during senescence.
Publication Title
SWI/SNF regulates a transcriptional program that induces senescence to prevent liver cancer.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The homeodomain transcription factor, Pdx-1, has important roles in pancreatic development and -cell function and survival. In the present study, we demonstrate that adenovirus-mediated overexpression of Pdx-1 in rat or human islets also stimulates cell replication. Moreover, co-overexpression of Pdx-1 with another homeodomain transcription factor, Nkx6.1, has an additive effect on proliferation compared to either factor alone, implying discrete activating mechanisms. Consistent with this, Nkx6.1 stimulates mainly -cell proliferation, whereas Pdx-1 stimulates both - and -cell proliferation. Furthermore, cyclins D1/D2 are upregulated by Pdx-1 but not by Nkx6.1, and inhibition of cdk4 blocks Pdx-1- but not Nkx6.1-stimulated islet cell proliferation. Genes regulated by Pdx-1 and not Nkx6.1 were identified by microarray analysis. Two members of the transient receptor potential cation (TRPC) channel family, TRPC3 and TRPC6, are upregulated by Pdx-1 overexpression, and siRNA-mediated knockdown of TRPC3/6 or TRPC6 alone inhibits Pdx-1-induced but not Nkx6.1-induced islet cell proliferation. Pdx-1 also stimulates ERK1/2 phosphorylation, an effect partially blocked by knockdown of TRPC3/6, and blockade of ERK1/2 activation with a MEK1/2 inhibitor partially impairs Pdx-1-stimulated proliferation. These studies define a pathway by which overexpression of Pdx-1 activates islet cell proliferation that is distinct from and additive to a pathway activated by Nkx6.1.
Publication Title
Pdx-1 activates islet α- and β-cell proliferation via a mechanism regulated by transient receptor potential cation channels 3 and 6 and extracellular signal-regulated kinases 1 and 2.
Sample Metadata Fields
Sex, Age, Specimen part
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GSE55079- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Loss of functional -cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. Nkx6.1 induces -cell proliferation, but the pathway by which Nkx6.1 activates -cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated -cell proliferation. Overexpression of the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Loss of functional -cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor Nkx6.1 in rat pancreatic islets induces -cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates -cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated -cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in -cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c, resulting in degradation of the cell cycle inhibitor p21CIP1. These studies identify a new bipartite pathway for activation of -cell proliferation, suggesting several new targets for expansion of functional -cell mass.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Genome occupancy profiling by high throughput sequencing Overall design: PolyA selected RNA-seq for shRNA-expressing MLL-AF9 transformed acute myeloid leukemia cells (RN2)
Publication Title
BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Most mammalian transcription factors and cofactors occupy thousands of genomic sites and modulate the expression of large gene networks to implement their biological functions. In this study, we describe an exception to this paradigm. TRIM33 is identified here as a lineage dependency in B cell neoplasms and is shown to perform this essential function by associating with a single cis element. ChIP-seq analysis of TRIM33 in murine B cell leukemia revealed a preferential association with two lineage-specific enhancers that harbor an exceptional density of motifs recognized by the PU.1 transcription factor. TRIM33 is recruited to these elements by PU.1, yet acts to antagonize PU.1 function. One of the PU.1/TRIM33 co-occupied enhancers is upstream of the pro-apoptotic gene Bim, and deleting this enhancer renders TRIM33 dispensable for leukemia cell survival. These findings reveal an essential role for TRIM33 in preventing apoptosis in B lymphoblastic leukemia by interfering with enhancer-mediated Bim activation. Overall design: RNA-Seq for shRNAs targeting Trim33 expressing B-ALL
Publication Title
The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, is primarily expressed on cells of the myeloid lineage, and to a lesser extent on endothelial cells and neurons in brain. Previous work demonstrated C5aR1 antagonist, PMX205, decreased amyloid pathology and suppressed cognitive deficits in Alzheimer Disease (AD) mouse models. In the Arctic AD mouse model, genetic deletion of C5aR1 prevented behavior deficits at 10 months. However, the molecular mechanisms of this protection has not been definitively demonstrated. To understand the role of microglial C5aR1 in the Arctic AD mouse model, we have taken advantage of the CX3CR1GFP and CCR2RFP reporter mice to distinguish microglia as GFP-positive and infiltrating monocytes as GFP and RFP positive, for subsequent transcriptome analysis on specifically sorted myeloid populations from wild type and AD mouse models. Immunohistochemical analysis of mice aged to 2, 5, 7 and 10 months showed no change in amyloid beta (Ab) deposition in the Arctic C5aR1 knockout (KO) mice relative to that seen in the Arctic mice. Of importance, no CCR2+ monocytes/macrophages were found near the plaques in the Arctic brain with or without C5aR1. RNA-seq analysis on microglia from these mice identified inflammation related genes as differentially expressed, with increased expression in the Arctic mice relative to wildtype and decreased expression in the Arctic/C5aR1KO relative to Arctic. In addition, phagosomal-lysosomal proteins and protein degradation pathways that were increased in the Arctic mice were further increased in the Arctic/C5aR1KO mice. These data are consistent with a microglial polarization state with restricted induction of inflammatory genes and enhancement of clearance pathways. Overall design: Microglia mRNA profiles of wildtype (WT), C5aR1 knockout (C5aR1KO), Arctic (ARC) and Arctic C5aR1 knockout (ARCKO) mice at 2, 5, 7 and 10-11 month. Duplicates were sequenced for each genotype on Illumina HiSeq 2500 platform.
Publication Title
Prevention of C5aR1 signaling delays microglial inflammatory polarization, favors clearance pathways and suppresses cognitive loss.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
The encapsulated yeast Cryptococcus neoformans can cause a fatal meningoencephalitis in immunocompromised patients. C. neoformans infection is acquired through the respiratory tract, but the cellular and molecular mechanisms of the pulmonary innate immune response are still not well defined. To investigate the response of CCR2+ inflammatory monocytes to C. neoformans, we compared the transcriptomes of CCR2+ inflammatory monocytes from the lungs of naïve versus infected mice. Overall design: Sorted pulmonary CCR2+ inflammatory monocytes were pooled from 6-7 CCR2-GFP reporter mice per group, including naïve mice and mice challenged with intratracheal Cryptococcus neoformans on days 5 and 10 post-infection.
Publication Title
Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The transcriptome of the three atino80 allelic mutants was compared to that of wild-type and 50B Arabidopsis plants (see Fritsch et al. 2004). Since the transcriptomes of 50B and wild-type plants were found to be identical, we compared expression in the mutant with 50B and with wild-type without distinction. Therefore, we had four replicates of the wild type condition (50B line, wild-type) and two replicates for each of the mutant alleles (atino80-1, atino80-2 and atino80-3), all ecotype Columbia. All lines were profiled in duplicate (grown independently at 2-week-intervals).
Publication Title
The INO80 protein controls homologous recombination in Arabidopsis thaliana.
Sample Metadata Fields
Age, Specimen part
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